scholarly journals Administration of Lactobacillus paracasei HB89 mitigates PM2.5-induced enhancement of inflammation and allergic airway response in murine asthma model

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243062
Author(s):  
Ching-Hung Lin ◽  
Chia-Yi Tseng ◽  
Ming-Wei Chao
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
White Blood Cells ◽  
Lactobacillus Paracasei ◽  
Animal Blood ◽  
Abnormal Immune Response ◽  
Asthma Model ◽  
Cell Counts ◽  
Airway Response ◽  
Ige Response

PM2.5 causes abnormal immune response and asthma in animals. In this study, a Balb/c mouse animal model was exposed to PM2.5 to induce asthma. Lactobacillus paracasei HB89 was fed at the same time, in order to observe whether L. paracasei HB89 mitigates respiratory tract allergies stimulated by PM2.5. The results showed that PM2.5 stimulated a significant increase in white blood cells and immunoglobulin (IgE) in OVA-induced allergic Balb/c mice, and IgE in the blood further triggered the release of histamine in the lung immune cells. This not only increased overall immune cell counts, but the lymphocyte counts also increased significantly, resulting in significant inhibitions of cytokines INF-r and TGF-β, and induction of IL-4, IL-5, IL-13 and IL-17a. After feeding with HB89, apart from the absence of observable changes in body weight, the total white blood cell count in the animal blood and IgE response were also be reduced; the proliferation of immune cells in the lungs caused by PM2.5 was slowed down; and histamine and cytokines INF-r and TGF-β were secreted in large quantities, but IL- 4, IL-5, IL-13, IL-17a were inhibited, which effectively reduced the possibility of asthma induction.

scholarly journals GABAA receptor α4-subunit knockout enhances lung inflammation and airway reactivity in a murine asthma model

2017 ◽  
Vol 313 (2) ◽  
pp. L406-L415 ◽  
Author(s):  
Gene T. Yocum ◽  
Damian L. Turner ◽  
Jennifer Danielsson ◽  
Matthew B. Barajas ◽  
Yi Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Immune Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Asthma Model

Emerging evidence indicates that hypnotic anesthetics affect immune function. Many anesthetics potentiate γ-aminobutyric acid A receptor (GABAAR) activation, and these receptors are expressed on multiple subtypes of immune cells, providing a potential mechanistic link. Like immune cells, airway smooth muscle (ASM) cells also express GABAARs, particularly isoforms containing α4-subunits, and activation of these receptors leads to ASM relaxation. We sought to determine if GABAAR signaling modulates the ASM contractile and inflammatory phenotype of a murine allergic asthma model utilizing GABAAR α4-subunit global knockout (KO; Gabra40/0) mice. Wild-type (WT) and Gabra4 KO mice were sensitized with house dust mite (HDM) antigen or exposed to PBS intranasally 5 days/wk for 3 wk. Ex vivo tracheal rings from HDM-sensitized WT and Gabra4 KO mice exhibited similar magnitudes of acetylcholine-induced contractile force and isoproterenol-induced relaxation ( P = not significant; n = 4). In contrast, in vivo airway resistance (flexiVent) was significantly increased in Gabra4 KO mice ( P < 0.05, n = 8). Moreover, the Gabra4 KO mice demonstrated increased eosinophilic lung infiltration ( P < 0.05; n = 4) and increased markers of lung T-cell activation/memory (CD62L low, CD44 high; P < 0.01, n = 4). In vitro, Gabra4 KO CD4+ cells produced increased cytokines and exhibited increased proliferation after stimulation of the T-cell receptor as compared with WT CD4+ cells. These data suggest that the GABAAR α4-subunit plays a role in immune cell function during allergic lung sensitization. Thus GABAAR α4-subunit-specific agonists have the therapeutic potential to treat asthma via two mechanisms: direct ASM relaxation and inhibition of airway inflammation.

scholarly journals Simulated bacterial infection disrupts the circadian fluctuation of immune cells in wrinkle-lipped bats (Chaerephon plicatus)

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3570 ◽  
Author(s):  
Philipp Weise ◽  
Gábor A. Czirják ◽  
Oliver Lindecke ◽  
Sara Bumrungsri ◽  
Christian C. Voigt
Keyword(s):  
Bacterial Infection ◽  
Immune Cells ◽  
Immune Cell ◽  
Experimental Treatment ◽  
Cell Types ◽  
Diurnal Fluctuation ◽  
Control Group ◽  
Carrier Liquid ◽  
Cell Counts ◽  
Body Mass Changes

BackgroundLeukocyte concentrations follow a circadian pattern in mammals, with elevated values at times of potential contact with pathogens and parasites. We hypothesized that this pattern is disturbed after an immune challenge.MethodsIn Thailand, we captured wrinkle-lipped bats (Chaerephon plicatus), when they returned to their colony at dawn. We challenged half of the animals (experimental group) with bacterial lipopolysaccharides and treated the others only with the carrier liquid (control group). We then compared body mass changes and differences in circulating immune cell counts at 8 h post-treatment.ResultsIn experimental animals, we observed an increase in total leukocyte and neutrophil numbers of 17% and 95%, respectively. In control animals, concentrations of leukocytes decreased by 44% and those of neutrophils remained constant. Experimental treatment had no effect on lymphocytes, yet changes in eosinophil numbers were explained by sex. Eosinophils decreased by 66% in females and by 62% in males. Basophils and monocytes were rarest among all observed cell types and analysis was either impossible because of low numbers or yielded no significant effects, respectively.DiscussionOur findings show that a simulated bacterial infection triggered a neutrophil-associated immune response in wrinkle-lipped bats, indicating a disruption of the diurnal fluctuation of immune cells. Our study suggests that bats exhibit circadian rhythms in immune cell counts. The magnitude of these fluctuations may vary across species according to specific-specific infection risks associated with colony sizes or specific roosting habits.

Effects of Qigong on Immune Cells

2003 ◽  
Vol 31 (02) ◽  
pp. 327-335 ◽  
Author(s):  
Myeong Soo Lee ◽  
Hwa Jeong Huh ◽  
Seong Min Jeong ◽  
Hye-Sook Jang ◽  
Hoon Ryu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Blood Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
White Blood Cells ◽  
Post Intervention ◽  
Cell Numbers

The aim of this study was to investigate the influence of two acute Qigong interventions (Qi-training and Qi-therapy) on immune cells. The Qigong interventions were compared with placebo training and placebo therapy in which no attempt was made to gather or move Qi. Immune cell numbers were measured pre-intervention, immediately post-intervention and 1 or 2 hours post-intervention. White blood cells increased significantly 2 hours after actual Qi-training (p < 0.05) but not sham training compared with pre-intervention. There were significant increases in lymphocytes 2 hours after actual but not sham Qi-training (p < 0.05) and monocyte numbers were significantly increased immediately after both actual Qi-training (p < 0.01) and sham training (p < 0.05). NK cell numbers decreased significantly both immediately after Qi-training and after sham movements done without concomitant Qi-training (p < 0.01). There were no significant effects on neutrophils. Actual Qi-therapy but not sham therapy increased monocyte numbers immediately after Qi-therapy, and lymphocytes increased more after real than after sham therapy. Neutrophils were again little changed. The data indicate that a single Qigong intervention can increase the monocyte and lymphocyte numbers.

scholarly journals Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease

2021 ◽  
Vol 9 (2) ◽  
pp. e1125
Author(s):  
Rui Li ◽  
Thomas Francis Tropea ◽  
Laura Rosa Baratta ◽  
Leah Zuroff ◽  
Maria E. Diaz-Ortiz ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Parkinson Disease ◽  
B Cell ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Cell Counts

Background and ObjectivesThere has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.MethodsPeripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation). Comprehensive multicolor flow cytometry was performed on whole blood leukocytes and peripheral blood mononuclear cells to characterize different immune subsets and their ex vivo responses.ResultsThe discovery cohort included 17 NCs and 12 participants with PD, and the validation cohort included 18 NCs and 18 participants with PD. Among major immune cell types, B cells appeared to be preferentially affected in PD. Proliferating B cell counts were decreased in patients with PD compared with controls. Proportions of B-cell subsets with regulatory capacity such as transitional B cells were preferentially reduced in the patients with PD, whereas proportions of proinflammatory cytokine-producing B cells increased, resulting in a proinflammatory shift of their B-cell functional cytokine responses. Unsupervised principal component analysis revealed increased expression of TNFα and GM-CSF by both B cells and T cells of patients with PD. In addition, levels of follicular T cells, an important B-cell helper T-cell population, decreased in the patients with PD, correlating with their B-cell abnormality.DiscussionOur findings define a novel signature of peripheral immune cells and implicate aberrant Tfh:B-cell interactions in patients with PD.

scholarly journals An association between the gut microbiota and immune cell dynamics in humans

2019 ◽  
Author(s):  
Jonas Schluter ◽  
Jonathan U. Peled ◽  
Bradford P. Taylor ◽  
Melody Smith ◽  
Kate A. Markey ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Hematopoietic Cell Transplantation ◽  
Immune Cell ◽  
White Blood Cells ◽  
Anaerobic Bacteria ◽  
Human Immune System ◽  
Cell Dynamics ◽  
Cell Engraftment

ABSTRACTThe gut microbiota influences development and homeostasis of the mammalian immune system1–3, can alter immune cell compositions in mice4–7, and is associated with responses to immunotherapy that rely on the activity of peripheral immune cells8–12. Still, our understanding of how the microbiota modulates immune cells dynamics remains limited, particularly in humans where a lack of deliberate manipulations makes inference challenging. Here we study hundreds of hospitalized—and closely monitored—patients receiving hematopoietic cell transplantation as they recover from chemotherapy and stem cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously. We analyzed daily changes in white blood cells from 2,235 patients, and 10,680 longitudinal microbiota samples to identify bacteria associated with those changes. Bayesian inference and validation across patient cohorts revealed consistent associations between gut bacteria and white blood cell dynamics in the context of immunomodulatory medications, clinical metadata and homeostatic feedbacks. We contrasted the potency of fermentatively active, obligate anaerobic bacteria with that of medications with known immunomodulatory mechanism to estimate the potential of the microbiota to influence peripheral immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.

scholarly journals P02.08 The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A10.2-A11
Author(s):  
S Salmi ◽  
A Lin ◽  
B Hirschovits-Gerz ◽  
M Valkonen ◽  
N Aaltonen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factors ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Positive Association ◽  
Melanoma Cells ◽  
Cell Counts

BackgroundAlthough Malignant Cutaneous Melanoma (CM) is a highly immunogenic cancer, it can evade the immune system by forming an immunosuppressive tumor microenvironment (TME). FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) are a part of the immunosuppressive TME in CM. In previous studies, IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. To develop new therapeutic strategies, it is important to understand the role of immunosuppressive factors in CM.Materials and MethodsWe investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors, and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells was analysed quantitatively and the coverage and intensity of IDO+ tumor cells was evaluated semiquantitatively. Tumors were divided into IDO-negative and IDO-positive, containing less or more than 1% IDO+ melanoma cells of all tumor cells, respectively. P values equal to or less than 0.05 were considered statistically significant.ResultsIDO+ stromal immune cells and FoxP3+ Tregs mainly accumulated in the areas with lymphocyte infiltration and thus resided mostly in the perilesional stroma. The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence-free survival. We further showed that IDO-positive tumors contained significantly higher amounts of FoxP3+ Tregs and IDO+ stromal immune cells than IDO-negative tumors. However, the correlation between FoxP3+ Treg and IDO+ stromal immune cell counts was rather weak.ConclusionsOur results indicate that IDO expression is intimately involved in creating a TME conducive to tumor growth in CM. Thus, targeting IDO enzymatic pathway might be a worth of further studies in CM. Furthermore, we show that FoxP3+ Tregs appear to contribute to the immunosuppressive TME in CM, but their role may not be that critical to melanoma progression. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies. Support: Sigrid Juselius Foundation (S.P.-S.), Academy of Finland (S.P.-S.), The Paavo Koistinen Foundation (S.S.), Emil Aaltonen Foundation (S.S.) and North-Savo Cultural Foundation (S.S.).Disclosure InformationS. Salmi: None. A. Lin: None. B. Hirschovits-Gerz: None. M. Valkonen: None. N. Aaltonen: None. R. Sironen: None. H. Siiskonen: None. S. Pasonen-Seppänen: None.

scholarly journals Universally Available Innate and Adaptive Immune Cell Counts in Acute Ischemic Stroke (AIS) in the Context of Shared Pathobiology with COVID-19; Scoping Review

2021 ◽  
Author(s):  
Tissa Wijeratne ◽  
Carmela Sales ◽  
Rohit Menon ◽  
Leila Karimi ◽  
Mihajlo Jakovljevic
Keyword(s):  
Scoping Review ◽  
Immune Cells ◽  
Immune Cell ◽  
Stroke Recovery ◽  
Neutrophil Lymphocyte Ratio ◽  
Adaptive Immune ◽  
Adaptive Immune Cell ◽  
Cell Counts ◽  
Adaptive Immune Cells ◽  
Recovery Trajectory

Stroke is one of the leading cause of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of AIS, during the index event and during the repair process despite the limited attention drawn to this aspect in the existing stroke guidelines globally. The similar clinical course and similar circulating innate and adaptive immune cell counts in AIS and COVID-19 has created a renewed interest in these easily available biomarkers innate and adaptive immunological changes in AIS with potential diagnostic, prognostic, and therapeutic implications. The current scoping review aimed to assess the significance of circulating neutrophil and lymphocyte counts and their ratio (NLR) in AIS and explore their association with post-stroke recovery trajectory. The Arksey and O'Malley methodological framework was employed to review the published papers on the neutrophil-lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000-2020 were included in this scoping review. Fifty-three published papers were reviewed. This review's key finding is that a canonical inflammatory response occurs in AIS just as in the case of COVID-19 and neurological involvements well described in the recent literature. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes ) are associated with poorer outcomes during the acute interventions ( reperfusion therapies) as well as the recovery trajectory. Main representatives of innate and adaptive immunity follow a canonical course in AIS and COVID-19. Exaggerated circulating innate ( elevated neutrophils and elevated NLR) and reduced adaptive immune response (lymphopenia) correlate with the worse outcome in AIS and COVID-19. This scoping review's findings make the strongest case for a systems biology-based approach to the standard operating procedures in stroke care urgently.

Abstract W P235: The Nuclear Receptors FXR and Nur77 Exhibit Neuroprotective Effects in the Ischemic Mouse Brain

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jan-Kolja Strecker ◽  
Stephanie Hucke ◽  
Kai Diederich ◽  
Antje Schmidt ◽  
Luisa Klotz ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Nuclear Receptors ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Ischemic Lesion ◽  
Cell Counts

Introduction: FXR and Nur77, members of the nuclear hormone superfamily, have been shown to modulate pro- and anti-inflammatory responses by immune cells, such as macrophages or T cells. As ischemic stroke induces an inflammatory response accompanied by activation and recruitment of immune cells, the aim of this study was to investigate the influence of nuclear receptors Nur77, FXR as well as FXR activation by the agonist GW4064 in cerebral ischemia-reperfusion (I/R) injury. Methods: Transient middle cerebral ischemia (MCAO) was induced in adult mice assigned to 4 groups: placebo, Nur77-deficient, FXR-deficient and FXR-ligand GW4064-treated (each n=7-8). A priori survival-time was set to 72 hours. Mice underwent functional tests and histological studies were performed for evaluation of infarct volume, immune cell activation/immigration and neuronal apoptosis. Results: MCAO led to delayed (24-48h after I/R) but severely worsened functional outcome in Nur77 and FXR-ko mice compared to wildtype animals (p<0.001, ANOVA+Bonferroni post-hoc). FXR- and Nur77-ko mice developed increased infarct volumes (Nur77, p<0.05) and had elevated TUNEL+-cell counts within the ischemic lesion (FXR, p<0.05). In contrast, treatment with FXR-agonist GW4064 resulted in improved functional outcome compared to placebo-treated mice. Evaluation of microglia and monocytes/macrophages showed an increased F4/80+-cell count 72h following MCAO in GW4064-treated mice. Conclusion: Deficiency of nuclear receptors Nur77 and FXR significantly worsened functional outcome, increased infarct size and cell apoptosis, whereas treatment with nuclear receptor agonist GW4064 led to improved rotarod performance and altered F4/80+-immune cell response. These results suggest a crucial involvement of the nuclear receptors Nur77 and FXR in pathways relating to post-stroke inflammation and tissue damage development.

Day length affects immune cell numbers in deer mice: interactions with age, sex, and prenatal photoperiod

1994 ◽  
Vol 267 (2) ◽  
pp. R596-R601 ◽  
Author(s):  
J. M. Blom ◽  
J. M. Gerber ◽  
R. J. Nelson
Keyword(s):  
Blood Cell ◽  
Immune Function ◽  
Immune Cells ◽  
Immune Cell ◽  
Day Length ◽  
Deer Mice ◽  
Immune Systems ◽  
Short Day ◽  
Functional Perspective ◽  
Cell Counts

The extent to which day length affects immune function was examined in the present study. Three goals were pursued: 1) to confirm and extend the observation that the immune systems of adult deer mice (Peromyscus maniculatus) are responsive to changes in photoperiod, 2) to examine the development of the photoperiod-associated changes in immune function, and 3) to discover whether photoperiodic information transmitted to the young during gestation influences immune function. In experiment 1, adult mice housed in short days had higher white blood cell and lymphocyte numbers than their long-day cohorts. Red blood cell and differential cell counts did not differ between long- and short-day animals. No sex differences were observed in the pattern of immune responses to photoperiod. The effect of photoperiod on immune cells in prepubertal animals was examined in experiment 2; a similar pattern of results was obtained as that for experiment 1, suggesting that the photoperiodic effect on the immune system is not mediated by sex steroid hormones. Prenatal and postnatal photoperiodic effects on immune cells were examined in experiment 3; pups gestated in one day length were cross-fostered to mothers in the same day length conditions or to mothers maintained in the alternative day length. The results of experiment 3 suggested that photoperiodic information transmitted from the mother to the young in utero subsequently affected immune systems of the pups. Animals gestated in short day lengths displayed higher immune status throughout life than mice gestated in long days. These results are discussed from an adaptive functional perspective.

scholarly journals Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukemia using patient similarity networks

2020 ◽  
Author(s):  
Zuzana Mikulkova ◽  
Gayane Manukyan ◽  
Peter Turcsanyi ◽  
Renata Urbanova ◽  
Jakub Savara ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Immune Cells ◽  
Progressive Disease ◽  
Immune Cell ◽  
Lymphocytic Leukemia ◽  
Novel Agents ◽  
Cell Counts ◽  
Similarity Networks ◽  
Intermediate Monocytes ◽  
Activation Status

Abstract Background: The tissue microenvironment in chronic lymphocytic leukemia (CLL) plays a key role in promoting neoplastic cell survival, proliferation, and drug resistance. There is a lack of complex characterization of CLL blood microenvironment and its clinical impact. Methods: Immunophenotypic profiles of circulating immune cells in 244 CLL patients (untreated, n=123; novel agents, n=67; previous immunochemotherapy, n=54) and age/sex-matched healthy controls (n=52) were assessed using flow cytometry and analyzed by multivariate patient similarity networks (PSNs). Results: Our study revealed high inter-individual heterogeneity in distribution and activation status of bystander immune cells in CLL, depending on the bulk of CLL cells. High CLL counts were associated with low activation status on circulating monocytes, T and NK cells and vice versa low CLL counts with high activation of immune cells, reaching levels in controls. Regarding treatment, the highest activation of immune cells, particularly of intermediate and non-classical monocytes, was evident in patients treated with novel agents. Clustering and visualization using PSNs confirmed low activation of immune cells in progressive disease, irrespectively of IgHV status and Binet stage. Calculating time-to-event endpoint, patients with high intermediate monocytes (>5.4%), predominantly low activated, were associated with 2.5-fold higher likelihood (95% CI 1.421-4.403, P =0.002) of event than those with low percentage of intermediate monocytes. Conclusions: Activation of circulating immune cells are dependent on the CLL cell counts and used therapy, with the lowest activation in patients with progressive disease. Percentage and activation of intermediate monocytes could be of prognostic value in CLL.

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